New medical therapies have been practiced whereby a probe such as a needle, catheter, wire, etc. is inserted into the body to a specified anatomical location and destructive means are conveyed to nerves by means of the probe to irreversibly damage tissue in the nearby regions. The objective is to abolish nerve function in the specified anatomic location. The result is that abnormally functioning physiological processes can be terminated or modulated back into a normal range. Unfortunately such medical therapies are not always successful because there is no means to assess that the nervous activity has been successfully abolished.
An example is renal nerve ablation to relieve hypertension. Various studies have confirmed the relationship of renal nerve integrity with blood pressure regulation. In various renal ablation procedures, a catheter is introduced into a hypertensive patient's arterial vascular system and advanced into the renal artery. Renal nerves are located in the arterial wall and in regions adjacent to the artery. Destructive means are delivered to the renal artery wall to an extent intended to cause destruction of nerve activity. Destructive means include energy such as RF, ultrasound, laser or chemical agents. The objective is to abolish the renal sympathetic nerve activity. Such nerve activity is an important factor in the creation of hypertension and abolishment of the nerve activity reduces hypertension.
Unfortunately not all patients respond to this therapy. Renal nerve ablation procedures are often ineffective, and are caused by a poor probe/tissue interface. Accordingly, insufficient quantities of destructive means are delivered to the sympathetic nerve fibers transmitting along the renal artery. One reason is that the delivery of destructive means to the arterial wall does not have a feedback control mechanism to assess the destruction of the nerve activity. As a consequence an insufficient quantity of destructive means is delivered and nervous activity is not abolished. Clinicians therefore, require a means of improving the probe/tissue interface, and a technology to monitor the integrity of the nerve fibers passing through the arterial wall in order to confirm destruction of nerve activity prior to terminating therapy. Current technology for the destruction of sympathetic nerve activity does not provide practitioners with a feedback control mechanisms to detect when the desired nervous activity destruction is accomplished. Nerve destructive means are applied empirically without knowledge that the desired effect has been achieved.
It is known that ablation of the renal artery, with sufficient energy, is able to effect a reduction in both systolic and diastolic blood pressure. Current methods are said to be, from an engineering perspective, open loop; i.e., the methods used to effect renal denervation do not employ any way of measuring, in an acute clinical setting, the results of applied ablation energies. It is only after application of such energies and a period of time (3-12 months) that the effects of the procedure are known.
The two major components of the autonomic nervous system (ANS) are the sympathetic and the parasympathetic nerves. The standard means for monitoring autonomic nerve activity is situations such as described is to insert very small electrodes into the nerve body or adjacent to it. The nerve activity creates an electrical signal in the electrodes which is communicated to a monitoring means such that a clinician can assess nerve activity. This practice is called microneurography and its practical application is by inserting the electrodes transcutaneously to the desired anatomical location. This is not possible in the case of the ablation of many autonomic nerves proximate arteries, such as the renal artery, because the arteries and nerves are located within the abdomen and cannot be accessed transcutaneously with any reliability. Thus the autonomic nerve activity cannot be assessed in a practical or efficacious manner.
The autonomic nervous system is responsible for regulating the physiological processes of circulation, digestion, metabolism, reproduction, and respiration among others. The sympathetic nerves and parasympathetic nerves most often accompany the blood vessels supplying the body organs which they regulate. Examples of such include but are not limited to the following: (1) Nerves regulating liver function accompany the hepatic artery and the portal vein. (2) Nerves regulating the stomach accompany the gastroduodenal, the right gastroepiploic artery, and the left gastric artery. (3) Nerves regulating the spleen accompany the lineal artery. (4) Nerves from the superior mesenteric plexus accompany the superior mesenteric artery, where both the artery and the nerves branch to the pancreas, small intestine, and large intestine. (5) Nerves of the inferior mesenteric plexus accompany the inferior mesenteric artery and branch with the artery to supply the large intestine, the colon, and the rectum.
When monitoring ANS activity, one must generally differentiate between the electrical signals generated by the ANS and those generated by muscle activity, which is commonly called EMG. EMG signals possess amplitudes several orders of magnitude larger than compared to those of the ANS. Probes possessing electrodes have been used to assess the EMG of the heart, stomach, intestines, and other muscles of the body. Such probes and their means and methods for detecting and analyzing the electric signals are not suitable for use with signals generated by the ANS.
Deficiencies in the use of existing therapeutic protocols in denervation of autonomic nerves proximate arteries include: 1. The inability to determine the appropriate lesion sites along the artery that correspond to the track of nerves; 2. The inability to verify that the destructive devices are appropriately positioned on the arterial wall, normalizing the tissue/device interface and enabling energy transfer through the vessel wall, and 3. Inability to provide feedback to the clinician intraoperatively to describe lesion completeness or the integrity of the affected nerve fibers. As a consequence, current autonomic nerve ablation procedures are performed in a ‘blinded’ fashion; the clinician performing the procedure does not know where the nerves are located; and further, whether the nerves have truly been ablated. Instead, surrogates such as catecholamine spillover into the circulating blood have been used to attempt to evaluate the termination of autonomic nerve activity such as renal sympathetic nerve activity (RSNA). It is entirely likely that this deficiency could largely be responsible for the current questionable data coming from clinical trials in the US. Therefore, a system designed to indicate with precision, and in real time, whether ablation was successful is urgently needed.